[English] 日本語
Yorodumi
- PDB-5qu0: TGF-BETA RECEPTOR TYPE 1 KINASE DOMAIN (T204D) IN COMPLEX WITH 6-... -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 5qu0
TitleTGF-BETA RECEPTOR TYPE 1 KINASE DOMAIN (T204D) IN COMPLEX WITH 6-[4-(3-CHLORO-4-FLUOROPHENYL)-1-(2-HYDROXYETHYL)-1H-IMIDAZOL-5-YL]IMIDAZO[1,2-B]PYRIDAZINE-3-CARBONITRILE
ComponentsTGF-beta receptor type-1
KeywordsTRANSFERASE / ALK5 / KINASE DOMAIN / TRANSFERASE-TRANSFERASE INHIBITOR COMPLEX
Function / homology
Function and homology information


extracellular structure organization / epicardium morphogenesis / parathyroid gland development / transforming growth factor beta ligand-receptor complex / regulation of cardiac muscle cell proliferation / myofibroblast differentiation / positive regulation of tight junction disassembly / positive regulation of epithelial to mesenchymal transition involved in endocardial cushion formation / TGFBR2 Kinase Domain Mutants in Cancer / transforming growth factor beta receptor activity ...extracellular structure organization / epicardium morphogenesis / parathyroid gland development / transforming growth factor beta ligand-receptor complex / regulation of cardiac muscle cell proliferation / myofibroblast differentiation / positive regulation of tight junction disassembly / positive regulation of epithelial to mesenchymal transition involved in endocardial cushion formation / TGFBR2 Kinase Domain Mutants in Cancer / transforming growth factor beta receptor activity / positive regulation of mesenchymal stem cell proliferation / ventricular compact myocardium morphogenesis / SMAD2/3 Phosphorylation Motif Mutants in Cancer / TGFBR1 KD Mutants in Cancer / TGFBR3 regulates TGF-beta signaling / positive regulation of vasculature development / activin receptor activity, type I / regulation of epithelial to mesenchymal transition / cardiac epithelial to mesenchymal transition / activin receptor complex / mesenchymal cell differentiation / transforming growth factor beta receptor activity, type I / neuron fate commitment / positive regulation of extracellular matrix assembly / type II transforming growth factor beta receptor binding / angiogenesis involved in coronary vascular morphogenesis / receptor protein serine/threonine kinase / transmembrane receptor protein serine/threonine kinase activity / TGFBR1 LBD Mutants in Cancer / pharyngeal system development / activin binding / germ cell migration / coronary artery morphogenesis / activin receptor signaling pathway / ventricular trabecula myocardium morphogenesis / filopodium assembly / embryonic cranial skeleton morphogenesis / response to cholesterol / transforming growth factor beta binding / I-SMAD binding / negative regulation of chondrocyte differentiation / collagen fibril organization / endothelial cell activation / endothelial cell proliferation / skeletal system morphogenesis / lens development in camera-type eye / positive regulation of filopodium assembly / anterior/posterior pattern specification / artery morphogenesis / ventricular septum morphogenesis / roof of mouth development / negative regulation of endothelial cell proliferation / SMAD binding / TGF-beta receptor signaling activates SMADs / positive regulation of SMAD protein signal transduction / blastocyst development / regulation of protein ubiquitination / endothelial cell migration / bicellular tight junction / epithelial to mesenchymal transition / positive regulation of epithelial to mesenchymal transition / positive regulation of stress fiber assembly / cellular response to transforming growth factor beta stimulus / positive regulation of endothelial cell proliferation / transforming growth factor beta receptor signaling pathway / post-embryonic development / Downregulation of TGF-beta receptor signaling / thymus development / negative regulation of cell migration / TGF-beta receptor signaling in EMT (epithelial to mesenchymal transition) / skeletal system development / kidney development / cell motility / negative regulation of extrinsic apoptotic signaling pathway / positive regulation of apoptotic signaling pathway / wound healing / cellular response to growth factor stimulus / male gonad development / UCH proteinases / heart development / nervous system development / regulation of gene expression / peptidyl-serine phosphorylation / positive regulation of cell growth / in utero embryonic development / positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction / receptor complex / regulation of cell cycle / protein kinase activity / intracellular signal transduction / Ub-specific processing proteases / endosome / positive regulation of cell migration / membrane raft / protein serine/threonine kinase activity / ubiquitin protein ligase binding / positive regulation of cell population proliferation / regulation of DNA-templated transcription / positive regulation of gene expression / apoptotic process
Similarity search - Function
GS domain / Transforming growth factor beta type I GS-motif / GS domain profile. / GS motif / Activin types I and II receptor domain / Activin types I and II receptor domain / Ser/Thr protein kinase, TGFB receptor / Snake toxin-like superfamily / Transferase(Phosphotransferase) domain 1 / Transferase(Phosphotransferase); domain 1 ...GS domain / Transforming growth factor beta type I GS-motif / GS domain profile. / GS motif / Activin types I and II receptor domain / Activin types I and II receptor domain / Ser/Thr protein kinase, TGFB receptor / Snake toxin-like superfamily / Transferase(Phosphotransferase) domain 1 / Transferase(Phosphotransferase); domain 1 / Phosphorylase Kinase; domain 1 / Phosphorylase Kinase; domain 1 / Serine/threonine-protein kinase, active site / Serine/Threonine protein kinases active-site signature. / Protein kinase domain / Serine/Threonine protein kinases, catalytic domain / Protein kinase, ATP binding site / Protein kinases ATP-binding region signature. / Protein kinase domain profile. / Protein kinase domain / Protein kinase-like domain superfamily / 2-Layer Sandwich / Orthogonal Bundle / Mainly Alpha / Alpha Beta
Similarity search - Domain/homology
Chem-QMV / TGF-beta receptor type-1
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / molecular replacement / Resolution: 1.67 Å
AuthorsSheriff, S.
CitationJournal: Acs Med.Chem.Lett. / Year: 2020
Title: Discovery of BMS-986260, a Potent, Selective, and Orally Bioavailable TGF beta R1 Inhibitor as an Immuno-oncology Agent.
Authors: Velaparthi, U. / Darne, C.P. / Warrier, J. / Liu, P. / Rahaman, H. / Augustine-Rauch, K. / Parrish, K. / Yang, Z. / Swanson, J. / Brown, J. / Dhar, G. / Anandam, A. / Holenarsipur, V.K. / ...Authors: Velaparthi, U. / Darne, C.P. / Warrier, J. / Liu, P. / Rahaman, H. / Augustine-Rauch, K. / Parrish, K. / Yang, Z. / Swanson, J. / Brown, J. / Dhar, G. / Anandam, A. / Holenarsipur, V.K. / Palanisamy, K. / Wautlet, B.S. / Fereshteh, M.P. / Lippy, J. / Tebben, A.J. / Sheriff, S. / Ruzanov, M. / Yan, C. / Gupta, A. / Gupta, A.K. / Vetrichelvan, M. / Mathur, A. / Gelman, M. / Singh, R. / Kinsella, T. / Murtaza, A. / Fargnoli, J. / Vite, G. / Borzilleri, R.M.
History
DepositionNov 19, 2019Deposition site: RCSB / Processing site: RCSB
Revision 1.0Feb 5, 2020Provider: repository / Type: Initial release
Revision 1.1Mar 4, 2020Group: Data collection / Database references / Category: citation / citation_author
Item: _citation.journal_volume / _citation.page_first ..._citation.journal_volume / _citation.page_first / _citation.page_last / _citation.pdbx_database_id_PubMed / _citation.title
Revision 1.2May 12, 2021Group: Structure summary / Category: pdbx_deposit_group / Item: _pdbx_deposit_group.group_type
Revision 1.3Nov 17, 2021Group: Database references / Structure summary / Category: database_2 / pdbx_deposit_group
Item: _database_2.pdbx_DOI / _database_2.pdbx_database_accession ..._database_2.pdbx_DOI / _database_2.pdbx_database_accession / _pdbx_deposit_group.group_description / _pdbx_deposit_group.group_title
Revision 1.4May 22, 2024Group: Data collection / Category: chem_comp_atom / chem_comp_bond

-
Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

-
Assembly

Deposited unit
A: TGF-beta receptor type-1
hetero molecules


Theoretical massNumber of molelcules
Total (without water)35,6403
Polymers35,1651
Non-polymers4752
Water3,927218
1


  • Idetical with deposited unit
  • defined by author&software
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
MethodPISA
Unit cell
Length a, b, c (Å)41.730, 78.110, 90.470
Angle α, β, γ (deg.)90.000, 90.000, 90.000
Int Tables number19
Space group name H-MP212121

-
Components

#1: Protein TGF-beta receptor type-1 / TGFR-1 / Activin A receptor type II-like protein kinase of 53kD / Activin receptor-like kinase 5 / ...TGFR-1 / Activin A receptor type II-like protein kinase of 53kD / Activin receptor-like kinase 5 / ALK5 / Serine/threonine-protein kinase receptor R4 / SKR4 / TGF-beta type I receptor / Transforming growth factor-beta receptor type I / TbetaR-I


Mass: 35165.473 Da / Num. of mol.: 1 / Fragment: KINASE DOMAIN, UNP RESIDUES 200-503 / Mutation: YES
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: TGFBR1, ALK5, SKR4 / Plasmid: PFASTBAC1 / Production host: Spodoptera frugiperda (fall armyworm)
References: UniProt: P36897, receptor protein serine/threonine kinase
#2: Chemical ChemComp-QMV / 6-[4-(3-chloro-4-fluorophenyl)-1-(2-hydroxyethyl)-1H-imidazol-5-yl]imidazo[1,2-b]pyridazine-3-carbonitrile


Mass: 382.779 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C18H12ClFN6O / Feature type: SUBJECT OF INVESTIGATION
#3: Chemical ChemComp-GOL / GLYCEROL / GLYCERIN / PROPANE-1,2,3-TRIOL


Mass: 92.094 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Formula: C3H8O3
#4: Water ChemComp-HOH / water


Mass: 18.015 Da / Num. of mol.: 218 / Source method: isolated from a natural source / Formula: H2O
Has ligand of interestY

-
Experimental details

-
Experiment

ExperimentMethod: X-RAY DIFFRACTION / Number of used crystals: 1

-
Sample preparation

CrystalDensity Matthews: 2.1 Å3/Da / Density % sol: 41.33 %
Crystal growTemperature: 277 K / Method: vapor diffusion, hanging drop / pH: 5.6 / Details: 23%(w/v) PEG3350, 3%(v/v) glcyerol

-
Data collection

DiffractionMean temperature: 100 K
Diffraction sourceSource: SYNCHROTRON / Site: APS / Beamline: 17-ID / Wavelength: 1 / Wavelength: 1 Å
DetectorType: DECTRIS PILATUS 6M / Detector: PIXEL / Date: Jun 8, 2017
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 1 Å / Relative weight: 1
ReflectionResolution: 1.67→78.11 Å / Num. obs: 35314 / % possible obs: 100 % / Observed criterion σ(I): 0 / Redundancy: 6.5 % / Biso Wilson estimate: 20.09 Å2 / CC1/2: 0.998 / Rmerge(I) obs: 0.109 / Rpim(I) all: 0.046 / Rrim(I) all: 0.118 / Rsym value: 0.1 / Net I/σ(I): 11.5 / Num. measured all: 230437
Reflection shellResolution: 1.67→1.76 Å / Redundancy: 6.7 % / Rmerge(I) obs: 0.857 / Mean I/σ(I) obs: 2.2 / Num. measured all: 34127 / Num. unique all: 5078 / CC1/2: 0.759 / Rpim(I) all: 0.353 / Rrim(I) all: 0.928 / Rsym value: 0.793 / Net I/σ(I) obs: 2.2 / Rejects: 0 / % possible all: 100

-
Phasing

PhasingMethod: molecular replacement

-
Processing

Software
NameVersionClassificationNB
XDSdata reduction
Aimless0.5.31data scaling
AMoREphasing
BUSTER2.11.7refinement
PDB_EXTRACT3.22data extraction
RefinementMethod to determine structure: MOLECULAR REPLACEMENT
Starting model: 3TZM

3tzm


Resolution: 1.67→22.87 Å / Cor.coef. Fo:Fc: 0.95 / Cor.coef. Fo:Fc free: 0.935 / SU R Cruickshank DPI: 0.098 / Cross valid method: THROUGHOUT / σ(F): 0 / SU R Blow DPI: 0.103 / SU Rfree Blow DPI: 0.098 / SU Rfree Cruickshank DPI: 0.095
RfactorNum. reflection% reflectionSelection details
Rfree0.206 1723 4.92 %RANDOM
Rwork0.177 ---
obs0.178 35047 100 %-
Displacement parametersBiso max: 114.64 Å2 / Biso mean: 22.48 Å2 / Biso min: 7.63 Å2
Baniso -1Baniso -2Baniso -3
1-1.6848 Å20 Å20 Å2
2---4.2499 Å20 Å2
3---2.5651 Å2
Refine analyzeLuzzati coordinate error obs: 0.21 Å
Refinement stepCycle: final / Resolution: 1.67→22.87 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms2422 0 33 218 2673
Biso mean--22.04 28.98 -
Num. residues----306
Refine LS restraints
Refine-IDTypeNumberRestraint functionWeightDev ideal
X-RAY DIFFRACTIONt_dihedral_angle_d904SINUSOIDAL2
X-RAY DIFFRACTIONt_trig_c_planes57HARMONIC2
X-RAY DIFFRACTIONt_gen_planes413HARMONIC5
X-RAY DIFFRACTIONt_it2556HARMONIC20
X-RAY DIFFRACTIONt_nbd
X-RAY DIFFRACTIONt_improper_torsion
X-RAY DIFFRACTIONt_pseud_angle
X-RAY DIFFRACTIONt_chiral_improper_torsion326SEMIHARMONIC5
X-RAY DIFFRACTIONt_sum_occupancies
X-RAY DIFFRACTIONt_utility_distance
X-RAY DIFFRACTIONt_utility_angle
X-RAY DIFFRACTIONt_utility_torsion
X-RAY DIFFRACTIONt_ideal_dist_contact3228SEMIHARMONIC4
X-RAY DIFFRACTIONt_bond_d2556HARMONIC20.01
X-RAY DIFFRACTIONt_angle_deg3471HARMONIC20.99
X-RAY DIFFRACTIONt_omega_torsion3.6
X-RAY DIFFRACTIONt_other_torsion15.12
LS refinement shellResolution: 1.67→1.72 Å / Total num. of bins used: 18
RfactorNum. reflection% reflection
Rfree0.2403 127 4.55 %
Rwork0.2123 2665 -
all0.2136 2792 -
obs--100 %

+
About Yorodumi

-
News

-
Feb 9, 2022. New format data for meta-information of EMDB entries

New format data for meta-information of EMDB entries

  • Version 3 of the EMDB header file is now the official format.
  • The previous official version 1.9 will be removed from the archive.

Related info.:EMDB header

External links:wwPDB to switch to version 3 of the EMDB data model

-
Aug 12, 2020. Covid-19 info

Covid-19 info

URL: https://pdbj.org/emnavi/covid19.php

New page: Covid-19 featured information page in EM Navigator.

Related info.:Covid-19 info / Mar 5, 2020. Novel coronavirus structure data

+
Mar 5, 2020. Novel coronavirus structure data

Novel coronavirus structure data

Related info.:Yorodumi Speices / Aug 12, 2020. Covid-19 info

External links:COVID-19 featured content - PDBj / Molecule of the Month (242)：Coronavirus Proteases

+
Jan 31, 2019. EMDB accession codes are about to change! (news from PDBe EMDB page)

EMDB accession codes are about to change! (news from PDBe EMDB page)

  • The allocation of 4 digits for EMDB accession codes will soon come to an end. Whilst these codes will remain in use, new EMDB accession codes will include an additional digit and will expand incrementally as the available range of codes is exhausted. The current 4-digit format prefixed with “EMD-” (i.e. EMD-XXXX) will advance to a 5-digit format (i.e. EMD-XXXXX), and so on. It is currently estimated that the 4-digit codes will be depleted around Spring 2019, at which point the 5-digit format will come into force.
  • The EM Navigator/Yorodumi systems omit the EMD- prefix.

Related info.:Q: What is EMD? / ID/Accession-code notation in Yorodumi/EM Navigator

External links:EMDB Accession Codes are Changing Soon! / Contact to PDBj

+
Jul 12, 2017. Major update of PDB

Major update of PDB

  • wwPDB released updated PDB data conforming to the new PDBx/mmCIF dictionary.
  • This is a major update changing the version number from 4 to 5, and with Remediation, in which all the entries are updated.
  • In this update, many items about electron microscopy experimental information are reorganized (e.g. em_software).
  • Now, EM Navigator and Yorodumi are based on the updated data.

External links:wwPDB Remediation / Enriched Model Files Conforming to OneDep Data Standards Now Available in the PDB FTP Archive

-
Yorodumi

Thousand views of thousand structures

  • Yorodumi is a browser for structure data from EMDB, PDB, SASBDB, etc.
  • This page is also the successor to EM Navigator detail page, and also detail information page/front-end page for Omokage search.
  • The word "yorodu" (or yorozu) is an old Japanese word meaning "ten thousand". "mi" (miru) is to see.

Related info.:EMDB / PDB / SASBDB / Comparison of 3 databanks / Yorodumi Search / Aug 31, 2016. New EM Navigator & Yorodumi / Yorodumi Papers / Jmol/JSmol / Function and homology information / Changes in new EM Navigator and Yorodumi

Read more